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Effect of deep hypothermia and circulatory arrest on cerebral blood flow and metabolism
Effect of Deep Hypothermia and Circulatory Arrest on Cerebral Blood Flow and Metabolism William J. Greeley, MD, Frank H. Kern, MD, Jon N. Meliones, MD, and Ross M. Ungerleider, MD Departments of Anesthesiology, Pediatrics, and Surgery, Duke University Medical Center, Durham, North Carolina
The primary goal of monitoring cerebral blood flow and metabolism is to improve our understanding of the association with cardiopulmonary bypass and deep hypothermic circulatory arrest so that effective brain protection strategies can be developed and employed. A review of our cerebral blood flowkardiopulmonary bypass database, presently totaling 275 neonates and infants, for the purposes of this publication, reveals certain trends and some conclusions that can be drawn. Deep hypothermic circulatory arrest continues to be a factor in the delayed recovery of cerebral blood flow and metabolism in these patients. Examining flow and metabolism serially in the postoperative period shows that in the majority of patients, flow, metabolism and autoregulation return to normal within 24 hours after operation. Some patients' cerebral oxygen metabolism is unable to exert a protective response of increasing extraction in the
setting of low cerebral blood flow. We have also observed that in the setting of low cardiac output after cardiac repair, cerebral blood flow is low. It is therefore likely that low cardiac output and pressure-passive cerebral blood flow potentiate brain ischemia after cardiopulmonary bypass and operation in some patients. We have also examined in our series of 275 patients selective neuroprotection strategies for their potential for improving recovery of cerebral blood flow and cerebral metabolism. Duration of cooling on cardiopulmonary bypass correlates directly with suppression of metabolism due to hypothermia. Low-flow cardiopulmonary bypass instead of deep hypothermic circulatory arrest, and topical brain cooling with ice during deep hypothermic circulatory arrest, improve cerebral blood flow and cerebral metabolic recovery. (Ann Thorac Surg 1993;56:1464-6)
T
(cardiac output), perfusion pressure, temperature, hematocrit, and arterial carbon dioxide tension, a knowledge of the effect of these factors on the brain in neonates, infants, and children is essential. Furthermore, the examination of the brain under unusual biologic circumstances, such as after DHCA or during low-flow CPB at deep hypothermia (15" to 18°C) permits a unique opportunity to describe cerebrovascular physiology and pathophysiology. Estimates of CBF using transcranial Doppler echography [5] and xenon-133 clearance methods [6], cerebral metabolism by CMRO, [4] and near-infrared spectroscopic [7] methods, and cerebral function using processed electroencephalograms and evoked potentials have all provided new important information during pediatric cardiovascular operations. During CPB, hypothermia is the most important factor altering cerebral hemodynamics and metabolism. In a study of 67 patients, we noted that hypothermia produces a marked reduction in CBF, which decreases in a direct linear relationship with temperature [B]. In this study and in a companion study in adult cardiac patients [9], in which the major external factors manipulated by the extracorporeal circuit were evaluated, ie, carbon dioxide, perfusion pressure, pump flow rate, and temperature, temperature was the most important factor influencing CBF during CPB. In this same study in children [8], pressure/flow autoregulation or the ability to maintain a constant CBF despite wide ranges in mean arterial pressures was examined. We observed that during
he use of deep hypothermic cardiopulmonary bypass (CPB) with or without deep hypothermic circulatory arrest (DHCA) has substantially improved operating conditions for children undergoing congenital heart operations, resulting in improved survival and reduced cardiac morbidity. As overall surgical outcome has improved, neuropsychologic dysfunction has become a more prominent concern. Recent reports suggest that transient and permanent neuropsychologic dysfunction occur in some infants undergoing hypothermic CPB with or without total circulatory arrest [l].The occurrence of neuropsychologic impairment is becoming a major focal point for current research into the mechanisms of brain injury during CPB. Currently the most effective means of protecting the brain is hypothermia [2]. Hypothermia reduces cerebral blood flow (CBF) and metabolism (CMRO,), and preserves cellular stores of high-energy phosphates [3, 41. The primary goal of monitoring CBF and CMRO, is to improve our understanding of the association with CPB and DHCA so that effective brain protection strategies can be developed and employed. Because many of the determinants of normal brain perfusion become externally controlled by the cardiac team during CPB, eg, flow rate Presented at the International Symposium on Neurohumoral Effects of Profound Hypothermia in Infant Heart Surgery, London, England, March %19, 1993. Address reprint requests to Dr Greeley, Departments of Anesthesiology and Pediatrics, Duke University Medical Center, Durham, NC 27710.
0 1993 by The Society of Thoracic Surgeons
0003-4975/93/$6.00
Ann Thorac Surg 1993;56:1464-6
moderate hypothermic CPB (25" to 32"C), there was no association between CBF and mean arterial pressure. However, during deep hypothermic CPB (18' to 22"C), there was an association between CBF and mean arterial pressure. We concluded that during deep hypothermic temperatures, cerebral vascular resistance increases with temperature reduction. Cerebral vascular resistance remains high even when pump flow rates and perfusion pressure are substantially reduced. This loss of pressure/ flow autoregulation is most likely due to the influence of deep hypothermic temperatures on vascular reactivity. Severe temperature reductions impair vascular relaxation. This has been described as a cold-induced "cerebrovasoparesis" [8]. Whereas CBF decreases in a linear fashion with reductions in brain temperature, brain metabolism (CMRO,) decreases exponentially [4, 10, 111. In a study of 46 patients, we demonstrated that CMR02 is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children [4]. The increased metabolic suppression for younger patients may be due to a greater susceptibility of the immature neurons and glial elements to hypothermia or may reflect reduced brain mass and more efficient brain cooling. Cerebral blood flow decreases linearly with reductions in temperature. In contrast, CMRO, decreases exponentially with reductions in temperature. Therefore flow/metabolic ratios must increase with decreasing temperature during CPB in children. Elevated carbon dioxide tension is a potent cerebrovasodilator in both the awake and anesthetized state, with or without CPB. During CPB, multiple groups have independently shown that CBF increases with increasing arterial carbon dioxide tension [9, 121. We examined the effect of arterial carbon dioxide tension in 20 children [13]. In this study, the response to increases in carbon dioxide tension was diminished by two factors, deep hypothermia and age less than 1 year. The attenuated response of deep hypothermia is not surprising in view of the previous discussion of cold-induced cerebrovasoparesis [8, 131. Deep hypothermic circulatory arrest has also been examined by these methods and associated with a number of poorly understood effects on the brain in the immediate post-CPB period, including (1) reduced cerebral blood flow, ( 2 ) disordered brain metabolic activity, and (3) delayed functional recovery [4, 8, 14-17]. In a study of 67 patients, we directly measured CBF using xenon-133 clearance methods and CMRO, [8]. We demonstrated postischemic hypoperfusion and altered cerebral metabolism in these infants [4, 141. Studies using transcranial Doppler echography have also shown reduced cerebral blood flow velocity after DHCA [5]. Using near-infrared spectroscopy, we examined 15 patients and noted that brain tissue oxyhemoglobin levels and the oxidation state of cytochrome aa3 oxidase decreased significantly during circulatory arrest [ 161. After CPB, the cytochrome oxidation state and the CMRO, were significantly lower than control measurements, and brain tissue deoxyhemoglobin level was elevated. Results of this study indicated that intracellular brain oxygenation decreases significantly
HYPOTHERMIA GREELEY ET AL BYPASS AND CEREBRAL BLOOD FLOW
1465
during circulatory arrest and remains impaired after rewarming and CPB despite normalization of oxygen availability. Extensive clinical experience using DHCA has shown the safe circulatory arrest period to be approximately 45 to 60 minutes [MI. Beyond this duration, the incidence of permanent and transient neurologic sequelae may be increased. New clinical evidence from CBFKMRO, and near-infrared spectroscopic measurements detailed above, magnetic resonance imaging [19], and experimental measurements of brain tissue pH, oxygen tension, and carbon dioxide tension [20, 211 all suggest that the brain continues to metabolize at a very low basal rate during DHCA. Presumably this basal metabolism is necessary for the preservation of cellular integrity. Metabolism continues until all adenosine triphosphate stores are depleted. At this point basal metabolism ceases, cellular integnty can no longer be maintained, and cerebral injury may ensue. Reports of the association of increasing duration of DHCA and worsening neurohistopathologic or metabolic recovery suggest that DHCA participates directly as a cause of injury. The lack of substrate delivery (oxygen, glucose) adversely affects the cellular level of high-energy compounds. This has been proposed as a possible mechanism for direct brain injury [22]. A review of our CBFKPB database, presently totalling 275 patients, for the purposes of this publication, reveals certain trends and some conclusions that can be drawn. Deep hypothermic circulatory arrest continues to be a factor in the delayed recovery of CBF and CMRO, in these patients. Examining flow and metabolism serially in the postoperative period shows that in the majority of patients, flow, metabolism, and autoregulation return to normal within 24 hours after operation. Observing the arteriovenous oxygen gradient across the brain and jugular venous bulb saturations in the DHCA patients, variable trends are seen. Some patients exhibit a normal response to low CBF, ie, increased oxygen extraction demonstrated by an increased gradient and decreased cerebral venous saturation. In some other patients with reduced CBF, there is limited ability to extract oxygen as demonstrated by a low arteriovenous oxygen gradient across the brain and a high jugular venous bulb saturation. This finding suggests that in some patients CMRO, is stunned and unable to exert a protective response of increasing extraction in the setting of low CBF. We have also observed that in the setting of low cardiac output after cardiac repair, CBF is low. It is therefore likely that low cardiac output and pressure-passive CBF potentiate brain ischemia after CPB and operation in some patients. We have also examined in our series of 275 patients selective neuroprotection strategies for their potential for improving recovery of CBF and CMRO,. Duration of cooling on CPB correlates directly with suppression of metabolism due to hypothermia. A longer cooling period (20 versus 12 minutes) promoted greater suppression and, presumably, enhanced protection. Low-flow CPB instead of DHCA and topical brain cooling with ice during DHCA improve CBF and cerebral metabolic recovery. Enhancing oxygen delivery after DHCA by increasing CPB pump
1466
HYPOTHERMIA GREELEY ET AL BYPASS AND CEREBRAL BLOOD FLOW
flow rate during rewarming did not promote restoration of CBF and metabolism after CPB. In summary, there is no doubt that CPB, especially deep hypothermic CPB, and DHCA affect brain blood flow, metabolism, and function. The question as to whether their effects are truly detrimental await further outcome studies. The data strongly suggest, however, that deep hypothermic CPB and DHCA may be detrimental to the brain under certain circumstances and if improperly implemented for a prolonged period of time. In young patients, who are now able to survive well into their adulthood because of the improvements in cardiac surgery, lifelong brain dysfunction is a significant disability.
References 1. Ferry PC. Neurologic sequelae of open-heart surgery in children. An “irritating question.” Am J Dis Child 1990;144: 369-73. 2. Michenfelder JD. In Michenfelder JD, ed. Anesthesia and the brain. New York: Churchill Livingstone, 1988:23-34. 3. Nonvood WI, Nonvood CR, Ingwall JS, Castenada AR, Fossel ET. Hypothermic circulatory arrest: 31-phosphorus nuclear magnetic resonance of isolated perfused neonatal rat brain. J Thorac Cardiovasc Surg 1979;78:823-30. 4. Greeley WJ, Kern FH, Ungerleider RM, et al. The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children. J Thorac Cardiovasc Surg 1991;101:78?-94. 5. Hillier SC, Burrows FA, Bissonnette B, Taylor RH. Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: assessment by transcranial Doppler sonography. Anesth Analg 1991;72:723-8. 6. Greeley W, Bushman G, Kong D, et al. Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. J Thorac Cardiovasc Surg 1988;95: 842-9. 7. Greeley WJ, Bracey VA, Ungerleider RM, et al. Recovery of cerebral metabolism and mitochondria1 oxidation state is delayed after hypothermic circulatory arrest. Circulation 1991;84(Suppl 3):400-15. 8. Greeley WJ, Ungerleider RM, Kern FH, et al. Effects of cardiopulmonary bypass on cerebral blood flow in neonates, infants, and children. Circulation 1989;80:1209-15. 9. Govier AV, Reves JG, McKay RD, et al. Factors and their
Ann Thorac Surg 1993;561461-6
influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg 1984;38:592-600. 10. Michenfelder JD,Theye RA. Hypothermia: effect of canine brain and whole-body metabolism. Anesthesiology 1968;29: 1107-13. 11. Croughwell N, Smith LR, Quill T, et al. The effect of temperature on cerebral metabolism and blood flow in adults dunng cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:549-54. 12. Prough DS, Stump DA, Roy RC, et al. Response of cerebral blood flow to changes in carbon dioxide tension during hypothermic cardiopulmonary bypass. Anesthesiology 1986; 64576431. 13. Kern FH, Ungerleider RM, Quill TJ, et al. Cerebral blood flow response to changes in PaCO, during hypothermic cardiopulmonarv bypass in children. I Thorac Cardiovasc Sure: i99i;ioi:iis-ii. 14. Greelev WT. Uneerleider RM. Smith LR. Reves IG. The effects of deip hypotYhermic cardiopulmona’ry bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg 1989;97:737-45. 15. Fisk G, Wright J, Hicks R, et al. The influence of duration of circulatory arrest at 20°C on cerebral changes. Anaesth Intensive Care 1976;4:126-34. 16. Greeley W, Bracey V, Ungerleider R, et al. Recovery of cerebral metabolism and mitochrondrial oxidation state are delayed after hypothermic circulatory arrest. Circulation 1991;82:412-8. 17. Weiss M, Weiss J, Cotton J, et al. A study of the electroencephalogram during surgery with deep hypothermia and circulatory arrest in infants. J Thorac Cardiovasc Surg 1975; 70:316-29. 18. Kirklin JW, Barratt-Boyes BG, eds. Cardiac surgery. New York: Wiley, 1993. 19. Swain JA, McDonald TJ, Griffith PK, et al. Low flow hypothermic cardiopulmonary bypass protects the brain. J Thorac Cardiovasc Surg 1991;102:76434. 20. Watanabe T, Orita H, Kobayashi M, Washio M. Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Comparative study of circulatory arrest, nonpulsatile low-flow perfusion, and pulsatile low-flow perfusion. J Thorac Cardiovasc Surg 1989;97396-401. 21. Watanabe T, Miura M, Orita H, et al. Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion. J Thorac Cardiovasc Surg 1990;100:274-80. 22. Greeley WJ. Con: Deep hypothermic circulatory arrest must be used selectively and discretely. J Cardiothorac Vasc Sure: 1991;5:638-41. Y
The primary goal of monitoring cerebral blood flow and metabolism is to improve our understanding of the association with cardiopulmonary bypass and deep hypothermic circulatory arrest so that effective brain protection strategies can be developed and employed. A review of our cerebral blood flowkardiopulmonary bypass database, presently totaling 275 neonates and infants, for the purposes of this publication, reveals certain trends and some conclusions that can be drawn. Deep hypothermic circulatory arrest continues to be a factor in the delayed recovery of cerebral blood flow and metabolism in these patients. Examining flow and metabolism serially in the postoperative period shows that in the majority of patients, flow, metabolism and autoregulation return to normal within 24 hours after operation. Some patients' cerebral oxygen metabolism is unable to exert a protective response of increasing extraction in the
setting of low cerebral blood flow. We have also observed that in the setting of low cardiac output after cardiac repair, cerebral blood flow is low. It is therefore likely that low cardiac output and pressure-passive cerebral blood flow potentiate brain ischemia after cardiopulmonary bypass and operation in some patients. We have also examined in our series of 275 patients selective neuroprotection strategies for their potential for improving recovery of cerebral blood flow and cerebral metabolism. Duration of cooling on cardiopulmonary bypass correlates directly with suppression of metabolism due to hypothermia. Low-flow cardiopulmonary bypass instead of deep hypothermic circulatory arrest, and topical brain cooling with ice during deep hypothermic circulatory arrest, improve cerebral blood flow and cerebral metabolic recovery. (Ann Thorac Surg 1993;56:1464-6)
T
(cardiac output), perfusion pressure, temperature, hematocrit, and arterial carbon dioxide tension, a knowledge of the effect of these factors on the brain in neonates, infants, and children is essential. Furthermore, the examination of the brain under unusual biologic circumstances, such as after DHCA or during low-flow CPB at deep hypothermia (15" to 18°C) permits a unique opportunity to describe cerebrovascular physiology and pathophysiology. Estimates of CBF using transcranial Doppler echography [5] and xenon-133 clearance methods [6], cerebral metabolism by CMRO, [4] and near-infrared spectroscopic [7] methods, and cerebral function using processed electroencephalograms and evoked potentials have all provided new important information during pediatric cardiovascular operations. During CPB, hypothermia is the most important factor altering cerebral hemodynamics and metabolism. In a study of 67 patients, we noted that hypothermia produces a marked reduction in CBF, which decreases in a direct linear relationship with temperature [B]. In this study and in a companion study in adult cardiac patients [9], in which the major external factors manipulated by the extracorporeal circuit were evaluated, ie, carbon dioxide, perfusion pressure, pump flow rate, and temperature, temperature was the most important factor influencing CBF during CPB. In this same study in children [8], pressure/flow autoregulation or the ability to maintain a constant CBF despite wide ranges in mean arterial pressures was examined. We observed that during
he use of deep hypothermic cardiopulmonary bypass (CPB) with or without deep hypothermic circulatory arrest (DHCA) has substantially improved operating conditions for children undergoing congenital heart operations, resulting in improved survival and reduced cardiac morbidity. As overall surgical outcome has improved, neuropsychologic dysfunction has become a more prominent concern. Recent reports suggest that transient and permanent neuropsychologic dysfunction occur in some infants undergoing hypothermic CPB with or without total circulatory arrest [l].The occurrence of neuropsychologic impairment is becoming a major focal point for current research into the mechanisms of brain injury during CPB. Currently the most effective means of protecting the brain is hypothermia [2]. Hypothermia reduces cerebral blood flow (CBF) and metabolism (CMRO,), and preserves cellular stores of high-energy phosphates [3, 41. The primary goal of monitoring CBF and CMRO, is to improve our understanding of the association with CPB and DHCA so that effective brain protection strategies can be developed and employed. Because many of the determinants of normal brain perfusion become externally controlled by the cardiac team during CPB, eg, flow rate Presented at the International Symposium on Neurohumoral Effects of Profound Hypothermia in Infant Heart Surgery, London, England, March %19, 1993. Address reprint requests to Dr Greeley, Departments of Anesthesiology and Pediatrics, Duke University Medical Center, Durham, NC 27710.
0 1993 by The Society of Thoracic Surgeons
0003-4975/93/$6.00
Ann Thorac Surg 1993;56:1464-6
moderate hypothermic CPB (25" to 32"C), there was no association between CBF and mean arterial pressure. However, during deep hypothermic CPB (18' to 22"C), there was an association between CBF and mean arterial pressure. We concluded that during deep hypothermic temperatures, cerebral vascular resistance increases with temperature reduction. Cerebral vascular resistance remains high even when pump flow rates and perfusion pressure are substantially reduced. This loss of pressure/ flow autoregulation is most likely due to the influence of deep hypothermic temperatures on vascular reactivity. Severe temperature reductions impair vascular relaxation. This has been described as a cold-induced "cerebrovasoparesis" [8]. Whereas CBF decreases in a linear fashion with reductions in brain temperature, brain metabolism (CMRO,) decreases exponentially [4, 10, 111. In a study of 46 patients, we demonstrated that CMR02 is exponentially related to temperature during hypothermic bypass with a temperature coefficient of 3.65 in neonates infants and children [4]. The increased metabolic suppression for younger patients may be due to a greater susceptibility of the immature neurons and glial elements to hypothermia or may reflect reduced brain mass and more efficient brain cooling. Cerebral blood flow decreases linearly with reductions in temperature. In contrast, CMRO, decreases exponentially with reductions in temperature. Therefore flow/metabolic ratios must increase with decreasing temperature during CPB in children. Elevated carbon dioxide tension is a potent cerebrovasodilator in both the awake and anesthetized state, with or without CPB. During CPB, multiple groups have independently shown that CBF increases with increasing arterial carbon dioxide tension [9, 121. We examined the effect of arterial carbon dioxide tension in 20 children [13]. In this study, the response to increases in carbon dioxide tension was diminished by two factors, deep hypothermia and age less than 1 year. The attenuated response of deep hypothermia is not surprising in view of the previous discussion of cold-induced cerebrovasoparesis [8, 131. Deep hypothermic circulatory arrest has also been examined by these methods and associated with a number of poorly understood effects on the brain in the immediate post-CPB period, including (1) reduced cerebral blood flow, ( 2 ) disordered brain metabolic activity, and (3) delayed functional recovery [4, 8, 14-17]. In a study of 67 patients, we directly measured CBF using xenon-133 clearance methods and CMRO, [8]. We demonstrated postischemic hypoperfusion and altered cerebral metabolism in these infants [4, 141. Studies using transcranial Doppler echography have also shown reduced cerebral blood flow velocity after DHCA [5]. Using near-infrared spectroscopy, we examined 15 patients and noted that brain tissue oxyhemoglobin levels and the oxidation state of cytochrome aa3 oxidase decreased significantly during circulatory arrest [ 161. After CPB, the cytochrome oxidation state and the CMRO, were significantly lower than control measurements, and brain tissue deoxyhemoglobin level was elevated. Results of this study indicated that intracellular brain oxygenation decreases significantly
HYPOTHERMIA GREELEY ET AL BYPASS AND CEREBRAL BLOOD FLOW
1465
during circulatory arrest and remains impaired after rewarming and CPB despite normalization of oxygen availability. Extensive clinical experience using DHCA has shown the safe circulatory arrest period to be approximately 45 to 60 minutes [MI. Beyond this duration, the incidence of permanent and transient neurologic sequelae may be increased. New clinical evidence from CBFKMRO, and near-infrared spectroscopic measurements detailed above, magnetic resonance imaging [19], and experimental measurements of brain tissue pH, oxygen tension, and carbon dioxide tension [20, 211 all suggest that the brain continues to metabolize at a very low basal rate during DHCA. Presumably this basal metabolism is necessary for the preservation of cellular integrity. Metabolism continues until all adenosine triphosphate stores are depleted. At this point basal metabolism ceases, cellular integnty can no longer be maintained, and cerebral injury may ensue. Reports of the association of increasing duration of DHCA and worsening neurohistopathologic or metabolic recovery suggest that DHCA participates directly as a cause of injury. The lack of substrate delivery (oxygen, glucose) adversely affects the cellular level of high-energy compounds. This has been proposed as a possible mechanism for direct brain injury [22]. A review of our CBFKPB database, presently totalling 275 patients, for the purposes of this publication, reveals certain trends and some conclusions that can be drawn. Deep hypothermic circulatory arrest continues to be a factor in the delayed recovery of CBF and CMRO, in these patients. Examining flow and metabolism serially in the postoperative period shows that in the majority of patients, flow, metabolism, and autoregulation return to normal within 24 hours after operation. Observing the arteriovenous oxygen gradient across the brain and jugular venous bulb saturations in the DHCA patients, variable trends are seen. Some patients exhibit a normal response to low CBF, ie, increased oxygen extraction demonstrated by an increased gradient and decreased cerebral venous saturation. In some other patients with reduced CBF, there is limited ability to extract oxygen as demonstrated by a low arteriovenous oxygen gradient across the brain and a high jugular venous bulb saturation. This finding suggests that in some patients CMRO, is stunned and unable to exert a protective response of increasing extraction in the setting of low CBF. We have also observed that in the setting of low cardiac output after cardiac repair, CBF is low. It is therefore likely that low cardiac output and pressure-passive CBF potentiate brain ischemia after CPB and operation in some patients. We have also examined in our series of 275 patients selective neuroprotection strategies for their potential for improving recovery of CBF and CMRO,. Duration of cooling on CPB correlates directly with suppression of metabolism due to hypothermia. A longer cooling period (20 versus 12 minutes) promoted greater suppression and, presumably, enhanced protection. Low-flow CPB instead of DHCA and topical brain cooling with ice during DHCA improve CBF and cerebral metabolic recovery. Enhancing oxygen delivery after DHCA by increasing CPB pump
1466
HYPOTHERMIA GREELEY ET AL BYPASS AND CEREBRAL BLOOD FLOW
flow rate during rewarming did not promote restoration of CBF and metabolism after CPB. In summary, there is no doubt that CPB, especially deep hypothermic CPB, and DHCA affect brain blood flow, metabolism, and function. The question as to whether their effects are truly detrimental await further outcome studies. The data strongly suggest, however, that deep hypothermic CPB and DHCA may be detrimental to the brain under certain circumstances and if improperly implemented for a prolonged period of time. In young patients, who are now able to survive well into their adulthood because of the improvements in cardiac surgery, lifelong brain dysfunction is a significant disability.
References 1. Ferry PC. Neurologic sequelae of open-heart surgery in children. An “irritating question.” Am J Dis Child 1990;144: 369-73. 2. Michenfelder JD. In Michenfelder JD, ed. Anesthesia and the brain. New York: Churchill Livingstone, 1988:23-34. 3. Nonvood WI, Nonvood CR, Ingwall JS, Castenada AR, Fossel ET. Hypothermic circulatory arrest: 31-phosphorus nuclear magnetic resonance of isolated perfused neonatal rat brain. J Thorac Cardiovasc Surg 1979;78:823-30. 4. Greeley WJ, Kern FH, Ungerleider RM, et al. The effect of hypothermic cardiopulmonary bypass and total circulatory arrest on cerebral metabolism in neonates, infants, and children. J Thorac Cardiovasc Surg 1991;101:78?-94. 5. Hillier SC, Burrows FA, Bissonnette B, Taylor RH. Cerebral hemodynamics in neonates and infants undergoing cardiopulmonary bypass and profound hypothermic circulatory arrest: assessment by transcranial Doppler sonography. Anesth Analg 1991;72:723-8. 6. Greeley W, Bushman G, Kong D, et al. Effects of cardiopulmonary bypass on eicosanoid metabolism during pediatric cardiovascular surgery. J Thorac Cardiovasc Surg 1988;95: 842-9. 7. Greeley WJ, Bracey VA, Ungerleider RM, et al. Recovery of cerebral metabolism and mitochondria1 oxidation state is delayed after hypothermic circulatory arrest. Circulation 1991;84(Suppl 3):400-15. 8. Greeley WJ, Ungerleider RM, Kern FH, et al. Effects of cardiopulmonary bypass on cerebral blood flow in neonates, infants, and children. Circulation 1989;80:1209-15. 9. Govier AV, Reves JG, McKay RD, et al. Factors and their
Ann Thorac Surg 1993;561461-6
influence on regional cerebral blood flow during nonpulsatile cardiopulmonary bypass. Ann Thorac Surg 1984;38:592-600. 10. Michenfelder JD,Theye RA. Hypothermia: effect of canine brain and whole-body metabolism. Anesthesiology 1968;29: 1107-13. 11. Croughwell N, Smith LR, Quill T, et al. The effect of temperature on cerebral metabolism and blood flow in adults dunng cardiopulmonary bypass. J Thorac Cardiovasc Surg 1992;103:549-54. 12. Prough DS, Stump DA, Roy RC, et al. Response of cerebral blood flow to changes in carbon dioxide tension during hypothermic cardiopulmonary bypass. Anesthesiology 1986; 64576431. 13. Kern FH, Ungerleider RM, Quill TJ, et al. Cerebral blood flow response to changes in PaCO, during hypothermic cardiopulmonarv bypass in children. I Thorac Cardiovasc Sure: i99i;ioi:iis-ii. 14. Greelev WT. Uneerleider RM. Smith LR. Reves IG. The effects of deip hypotYhermic cardiopulmona’ry bypass and total circulatory arrest on cerebral blood flow in infants and children. J Thorac Cardiovasc Surg 1989;97:737-45. 15. Fisk G, Wright J, Hicks R, et al. The influence of duration of circulatory arrest at 20°C on cerebral changes. Anaesth Intensive Care 1976;4:126-34. 16. Greeley W, Bracey V, Ungerleider R, et al. Recovery of cerebral metabolism and mitochrondrial oxidation state are delayed after hypothermic circulatory arrest. Circulation 1991;82:412-8. 17. Weiss M, Weiss J, Cotton J, et al. A study of the electroencephalogram during surgery with deep hypothermia and circulatory arrest in infants. J Thorac Cardiovasc Surg 1975; 70:316-29. 18. Kirklin JW, Barratt-Boyes BG, eds. Cardiac surgery. New York: Wiley, 1993. 19. Swain JA, McDonald TJ, Griffith PK, et al. Low flow hypothermic cardiopulmonary bypass protects the brain. J Thorac Cardiovasc Surg 1991;102:76434. 20. Watanabe T, Orita H, Kobayashi M, Washio M. Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Comparative study of circulatory arrest, nonpulsatile low-flow perfusion, and pulsatile low-flow perfusion. J Thorac Cardiovasc Surg 1989;97396-401. 21. Watanabe T, Miura M, Orita H, et al. Brain tissue pH, oxygen tension, and carbon dioxide tension in profoundly hypothermic cardiopulmonary bypass. Pulsatile assistance for circulatory arrest, low-flow perfusion, and moderate-flow perfusion. J Thorac Cardiovasc Surg 1990;100:274-80. 22. Greeley WJ. Con: Deep hypothermic circulatory arrest must be used selectively and discretely. J Cardiothorac Vasc Sure: 1991;5:638-41. Y